Causal relationship between gut microbiota and brain microbleeds: a comprehensive Mendelian randomization study

Background: Considerable evidence has been reported that alterations in gut microbiota composition could cause cerebrovascular diseases. The microbiota-gut-brain axis also hinted at a possible contribution of the gut microbiota to cerebrovascular diseases. However, the causal association between the gut microbiome and the risk of brain microbleeds (BMB) is unclear. Methods We performed two-sample bidirectional Mendelian randomization (MR) utilizing the summary-level data of respective genome-wide association study (GWAS) for 211 gut microbial taxa and two BMB phenotypes to reveal the causal association between gut microbiota and BMB. Results We identified 7 causal relationships between genetic liability in the gut microbiome and any BMB, including those involving the genus Lachnospiraceae. We found 13 associations between genetic liability in the gut microbiome and lobar BMB. Moreover, we found 6 associations between genetic liability in the gut microbiome and deep infratentorial BMB. The bidirectional, heterogeneity, and pleiotropy analyses confirmed the robustness of MR results. Conclusion Our MR analysis revealed that the gut microbiota was causally associated with BMB and may be helpful in providing new insights for further mechanistic and clinical studies of microbiota-mediated cerebrovascular diseases.